A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.